OP0255 BIMEKIZUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND AN INADEQUATE RESPONSE TO TUMOUR NECROSIS FACTOR INHIBITORS: 16-WEEK EFFICACY &amp; SAFETY FROM BE COMPLETE, A PHASE 3, MULTICENTRE, RANDOMISED PLACEBO-CONTROLLED STUDY
Authors: J. F. Merola, I. McInnes, C. T. Ritchlin, P. J. Mease, R. B. M. Landewé, A. Asahina, Y. Tanaka, R. B. Warren, L. Gossec, D. D. Gladman, F. Behrens, B. Ink, D. Assudani, R. Bajracharya, J. Coarse, L. Coates
Journal: Annals of the Rheumatic Diseases (2022)

Background Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. BKZ has shown sustained efficacy and tolerability up to 152 wks in a phase 2b study in patients (pts) with active psoriatic arthritis (PsA). 1,2 Objectives To assess efficacy and safety of BKZ vs placebo (PBO) in pts with active PsA and prior inadequate tumour necrosis factor inhibitor (TNFi) response in the 16-wk pivotal phase 3 study, BE COMPLETE. Methods BE COMPLETE ( NCT03896581 ) comprises a 16-wk double-blind, PBO-controlled period. Pts were aged ≥18 yrs, had a diagnosis of adult-onset, active PsA with ≥3 tender joints and ≥3 swollen joints, and inadequate response or intolerance to treatment with 1 or 2 TNFi. Pts were randomised 2:1 to BKZ 160 mg Q4W or PBO. From Wk 16, pts were eligible to enter an open-label extension, receiving BKZ 160 mg Q4W. The primary endpoint was a ≥50% improvement in American College of Rheumatology response criteria (ACR50) at Wk 16. Primary and ranked secondary efficacy endpoints were assessed at Wk 16. Results Of 400 randomised pts (BKZ: 267; PBO: 133), 388 (97.0%) completed Wk 16 (BKZ: 263 [98.5%]; PBO: 125 [94.0%]). Baseline characteristics were comparable between groups: mean age 50.5 yrs, weight 86.0 kg, BMI 29.8 kg/m 2 , time since diagnosis 9.5 yrs; 47.5% pts were male. At Wk 16, the primary endpoint (ACR50: 43.4% BKZ vs 6.8% PBO; p&lt;0.001; Figure 1) and all ranked secondary endpoints (HAQ-DI CfB, PASI90, SF-36 PCS CfB and MDA response) were met (all p&lt;0.001; Table 1). The ACR50 response was rapid with separation from PBO observed from Wk 4 (nominal p&lt;0.001). Additional outcomes, including ACR20/70, TJC and SJC CfB, and PASI75/100, demonstrated numerical improvement with BKZ compared to PBO at Wk 16 (all nominal p&lt;0.001; Table 1). Table 1. Disease characteristics at baseline and efficacy at Wk 16 PBO N=133 BKZ 160 mg Q4W N=267 p value Baseline characteristics TJC mean (SD) 19.3 (14.2) 18.4 (13.5) - SJC mean (SD) 10.3 (8.2) 9.7 (7.5) - PtGA-PsA mean (SD) 63.0 (22.0) 60.5 (22.5) - PtAAP mean (SD) 61.7 (24.6) 58.3 (24.2) - Psoriasis BSA n (%) &lt;3% 45 (33.8) 91 (34.1) - ≥3 to ≤10% 63 (47.4) 109 (40.8) - &gt;10% 25 (18.8) 67 (25.1) - PASI a mean (SD) 8.5 (6.6) b 10.1 (9.1) c - Prior TNFi n (%) Inadequate response to 1 TNFi 103 (77.4) 204 (76.4) - Inadequate response to 2 TNFi 15 (11.3) 29 (10.9) - Intolerance to TNFi 15 (11.3) 34 (12.7) - Current cDMARDs n (%) 63 (47.4) 139 (52.1) - Ranked endpoints in hierarchical order ACR50 * [NRI] n (%) 9 (6.8) 116 (43.4) &lt;0.001 HAQ-DI CfB † [RBMI] mean (SE) –0.1 (0.0) –0.4 (0.0) &lt;0.001 PASI90 †a [NRI]n (%) 6 (6.8) b 121 (68.8) c &lt;0.001 SF-36 PCS CfB † [RBMI]mean (SE) 1.4 (0.7) 7.3 (0.5) &lt;0.001 MDA Response † [NRI]n (%) 8 (6.0) 118 (44.2) &lt;0.001 Other endpoints ACR20 † [NRI]n (%) 21 (15.8) 179 (67.0) &lt;0.001 ‡ ACR70 † [NRI] n (%) 1 (0.8) 71 (26.6) &lt;0.001 ‡ TJC CfB [MI] mean (SE) –2.4 (0.9) –10.9 (0.8) &lt;0.001 ‡ SJC CfB [MI] mean (SE) –2.0 (0.5) –7.0 (0.4) &lt;0.001 ‡ PASI75 a [NRI]n (%) 9 (10.2) b 145 (82.4) c &lt;0.001 ‡ PASI100 a [NRI]n (%) 4 (4.5) b 103 (58.5) c &lt;0.001 ‡ Randomised set (N=400). * Primary endpoint; † Secondary endpoint; ‡ Nominal p value. a In patients with ≥3% BSA with PSO at BL; b n=88; c n=176. Over 16 wks, 107/267 (40.1%) pts on BKZ had ≥1 TEAE vs 44/132 (33.3%) pts on PBO; the three most frequent TEAEs on BKZ were nasopharyngitis (BKZ: 3.7%; PBO: 0.8%), oral candidiasis (BKZ: 2.6%; PBO: 0%) and upper respiratory tract infection (BKZ: 2.2%; PBO: 1.5%). Incidence of SAEs was low (BKZ: 1.9%; PBO: 0%); none led to discontinuation. 2 pts on BKZ discontinued due to a TEAE (BKZ: 0.7%; PBO: 0%). No systemic candidiasis, cases of IBD, MACE, uveitis, VTE or deaths were reported. Conclusion Dual inhibition of IL-17A and IL-17F with BKZ in pts with active PsA and prior inadequate TNFi response resulted in rapid, clinically relevant and statistically significant improvements in efficacy outcomes vs PBO. No new safety signals were observed. 1,2 References [1]Ritchlin C.T. Lancet 2020;395(10222):427–40; 2. Coates L.C. Ann Rheum Dis 2021;80:779–80(POS1022). Acknowledgements This study was funded by UCB Pharma. Editorial services were provided by Costello Medical. Disclosure of Interests Joseph F. Merola Paid instructor for: Amgen, Abbvie, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma, Consultant of: Amgen, Abbvie, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB Pharma, Iain McInnes Consultant of: AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma, Grant/research support from: BMS, Boehringer Ingelheim, Celgene, Janssen, UCB Pharma, Christopher T. Ritchlin Consultant of: Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Amgen and UCB Pharma, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma, Robert B.M. Landewé Speakers bureau: Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Consultant of: Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth, Akihiko Asahina Grant/research support from: AbbVie, Amgen, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Consultant of: AbbVie, Ayumi, Daiichi-Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Grant/research support from: Asahi-Kasei, AbbVie, Boehringer-Ingelheim, Chugai, Corrona, Daiichi-Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda, Richard B. Warren Paid instructor for: Astellas, DiCE, GSK, and Union, Consultant of: AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma, Grant/research support from: AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB Pharma, Grant/research support from: Amgen, Galapagos, Lilly, Pfizer, and Sandoz, Dafna D Gladman Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Frank Behrens Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi, Barbara Ink Shareholder of: GSK, UCB Pharma, Employee of: UCB Pharma, Deepak Assudani Shareholder of: UCB Pharma, Employee of: UCB Pharma, Rajan Bajracharya Shareholder of: UCB Pharma, Employee of: UCB Pharma, Jason Coarse Shareholder of: UCB Pharma, Employee of: UCB Pharma, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma